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Serum levels of insulin-like growth factor-I,-II and insulin-like growth factor binding proteins-2 and-3 in children with acute lymphoblastic leukaemia

European Journal of Pediatrics volume 155, Article number: 81 (1996) Cite this article

Abstract

Abstract

The insulin-like growth factor (IGF) signaling pathway may be of importance for the proliferation of different tumours (e.g. breast cancer and Wilms tumour). The bioavailability of both IGF-I and IGF-II is regulated by specific IGF-binding proteins (IGFBPs). IGFBP-2 is the predominant binding protein during fetal life, where it is expressed in most tissues. In contrast, postnatally it is mainly released by specific cell types (hepatocytes, astroglia, kidney cells, prostate cells) and a range of tumour cell lines. Furthermore, phytohaemagglutinin stimulated normal lymphoblasts and malignant lymphoblasts express IGFBP-2. In order to investigate the IGF regulatory pathway in leukaemia serum levels of IGF-I, IGF-II, IGFBP-2 and IGFBP-3 were determined in 28 leukaemic children. Whereas serum levels of IGF-I (mean/range: −2.7/−0.1 to −6.7 SDS), IGF-II (−3.6 SDS/−1.3 to −8.7) and IGFBP-3 (−2.0/+2.2 to −7.1 SDS) were significantly decreased comparable to levels in growth hormone deficiency, IGFBP-2 levels (+4.0/−0.45 to +7.4 SDS) were found to be markedly elevated and inversely correlated to IGF-I (r=−0.51,P=0.013). After haematological remission upon chemotherapy all four parameters had normalized in the 16 re-investigated children. Similar findings have been observed in one boy with a relapse including CNS leukaemia.

Conclusion

This study demonstrates that the proliferation of malignant lymphoblasts (at diagnosis vs treatment) occurs in the presence of decreased serum levels of IGF-I, IGF-II and IGFBP-3 and that diminished production of these peptides may contribute to impaired growth. It further indicates that serum levels of IGFBP-2 may be directly related to the proliferation of lymphoblasts.

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Abbreviations

ALL :

acute lymphoblastic leukaemia

BFM :

Berlin Frankfurt Münster, protocol for the treatment of childhood ALL

GH :

growth hormone

IGF :

insulin-like growth factor

IGFBP :

insulin-like growth factor binding protein

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Author information

Affiliations

  1. Magdeburg, Zentrum für Kinderheilkunde, Otto-von-Guericke-Universität, Halberstadter Strasse 13, D-39120, Magdeburg, Germany

    Klaus L. Mohnike, Ute Kluba, Uwe Mittler, Volker Aumann & Peter Vorwerk

  2. Abteilung Allgemeine Pädiatrie und Onkologie, Universitäts-Kinderklinik Tübingen, Tübingen, Germany

    Werner F. Blum

Authors
  1. Klaus L. Mohnike
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  2. Ute Kluba
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  3. Uwe Mittler
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  4. Volker Aumann
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  5. Peter Vorwerk
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  6. Werner F. Blum
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Mohnike, K.L., Kluba, U., Mittler, U. et al. Serum levels of insulin-like growth factor-I,-II and insulin-like growth factor binding proteins-2 and-3 in children with acute lymphoblastic leukaemia. Eur J Pediatr 155, 81 (1996). https://doi.org/10.1007/BF02075755

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  • DOI: https://doi.org/10.1007/BF02075755

Key words

  • Growth regulation
  • Leukaemia
  • Radioimmunoassay
  • Insulin-like growth factors
  • Insulin-like growth factor-binding proteins